Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The selective serotonin reuptake inhibitors (SSRIs) are a tribute to the ingenuity of pharmacologists and designers of molecules. Not only do these drugs have remarkable selectivity for the reuptake of serotonin compared with other monoamines, but also they have a commendable lack of affinity for receptors including the serotonin receptor. In contrast, the classical tricyclic antidepressants (TCAs) are less specific in their pharmacological action. In addition to inhibiting the reuptake of serotonin, TCAs inhibit the uptake of noradrenaline, dopamine and tyramine, and antagonize cholinergic (muscarinic), adrenergic and histaminergic receptors. Moreover, TCAs have quinidine-like anti-arrhythmic activity and lower the seizure threshold. Clinical investigations have shown that the SSRIs have equivalent therapeutic efficacy compared with the TCAs in the treatment of depression. However, the pharmacological specificity of the SSRIs is a clinical advantage since they lack the propensity to cause dry mouth, blurred vision, urinary hesitancy, constipation, hypotension and arrhythmia. Furthermore, the SSRIs are relatively safe in overdosage. The similarities between the SSRIs are more obvious than their differences: all are highly potent and selective inhibitors of serotonin reuptake with efficacy in the treatment of depression. Nevertheless, each has a distinctive pharmacological profile. In this review the characteristics desired in an "ideal" antidepressant are examined, and the ways in which the TCAs and SSRIs fit this ideal are compared.
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PMID:Clinical implications of the pharmacology of serotonin reuptake inhibitors. 148 74

The safety of intravenous (IV) and oral ondansetron has been evaluated in over 7,000 cancer patients in world-wide clinical trials. In adult patients receiving single-day chemotherapy, the incidence of adverse events was 45% with IV ondansetron (n = 317) and 59% with metoclopramide (n = 279). Headache occurred in 17% of ondansetron patients and 10% of metoclopramide patients, whereas diarrhea symptoms were reported in 15% of the former and 29% of the latter. The incidence and types of adverse events were similar following three 0.15 mg/kg IV ondansetron doses and 8- or 32-mg single IV doses. There was a slight increase in the incidence of headache following a single 32-mg dose (25%) compared with a single 8-mg dose (18%) or three 0.15 mg/kg doses (18%). The safety profile of oral ondansetron was similar to that of the IV formulation. Following an 8-mg oral dose administered three times a day for 3 days, the most frequently reported adverse events were headache (21%), constipation (7%), and abdominal pain (5%). In a group of 209 pediatric patients receiving chemotherapy, the incidence of adverse events following IV and oral ondansetron was 19%. The most commonly reported adverse event was headache (4%). In comparative clinical trials, extrapyramidal symptoms were reported in 5% of the metoclopramide patients but none of the ondansetron patients. In open-label trials, two patients who received ondansetron reported symptoms consistent with, but not diagnostic of, extrapyramidal reactions. The incidence of vascular occlusive events and seizure disorders was identical for ondansetron and comparative agents. Serum transaminase values increased significantly in 6% to 8% of ondansetron patients and 2% of metoclopramide patients who received cisplatin. There was no apparent relationship between the dose of ondansetron administered and the incidence of increased transaminase abnormalities. However, there was an apparent relationship between the dose of cisplatin administered and the incidence of transaminase abnormalities. In patients who received non-cisplatin chemotherapy, there was no difference in serum transaminase values between oral ondansetron and placebo. These data demonstrate that ondansetron is better tolerated than metoclopramide and is safe for IV and oral administration to patients receiving chemotherapy. In addition, ondansetron is well tolerated when administered as a single 32-mg infusion over 15 minutes.
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PMID:Clinical safety of ondansetron. 148 79

A case of warfarin-induced intramural hematoma and hemorrhagic infarction of the small intestine is described, and the literature on this adverse effect is reviewed. A 32-year-old white woman who had been receiving warfarin and carbamazepine came to a clinic complaining of lower back and stomach pain. She had a history of iliofemoral deep venous thromboses and seizures. A pelvic sonogram showed a large quantity of fluid present. Her prothrombin time (PT) was 29.2 sec. Her hemoglobin concentration and hematocrit were within the normal ranges. The patient was admitted to the hospital when her back pain increased and she vomited. The warfarin was discontinued. On day 5 the patient was still having abdominal pain and nausea. Her hemoglobin concentration and hematocrit had fallen to 6.6 g/dL and 20%, although her PT had decreased to 12.5 sec. On the same day, the patient underwent an exploratory laparotomy, and an indurated and ischemic area of jejunum was found and resected. The pathology report indicated the presence of hemorrhage and infarction consistent with an anticoagulant-related disorder. About 100 cases of intramural hematoma of the small intestine induced by anticoagulant therapy have been reported. Most patients are white males about 60 years of age. The sites most frequently involved are the duodenum and proximal jejunum. Symptoms include constipation, nausea, vomiting, and abdominal pain. Laboratory test and radiological findings are fairly nonspecific, but when found together in a patient receiving an anticoagulant, the diagnosis can be made with some confidence. Management may be complicated by the bleeding disorder, the intestinal obstruction if present, and the original indication for warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Warfarin-induced intramural hematoma of the small intestine. 161 15

Clozapine is a neuroleptic agent whose structure consists of a dibenzodiazepine derivative with a piperazinyl side chain. It has been classified as an atypical neuroleptic drug due to its unique neuropharmacologic profile. Clozapine has a weak binding affinity for dopamine D-1 and D-2 receptors by its slightly greater preference for D-1 receptors, as noted with a D-1:D-2 receptor binding ratio of 1.3. Other neuroreceptors are involved, as the drug has potent binding affinity for serotonin receptors 5-HT1A and 5-HT2. Clozapine also has antihistaminic, anticholinergic, and alpha-adrenergic antagonistic properties. Electrophysiologic studies show that it differs from other typical neuroleptics in that its actions appear to be specific for the cortical-limbic dopamine A-10 tract. In animal paradigms, in contrast to typical neuroleptics, clozapine did not produce catalepsy and had only transient effects in antagonizing other dopamine agonists. The drug is rapidly absorbed orally with a bioavailability of 0.27. After a single oral dose the elimination half-life was approximately 8-10 hours, but with several doses it increased to 14.1 hours. The agent is extensively metabolized by hepatic microsomal enzymes that forms the N-desmethyl and N-oxide metabolites. It is an effective neuroleptic that has been studied in short-term and long-term clinical trials, and multicenter trials. Clozapine was superior to chlorpromazine in the treatment of refractory schizophrenia that failed to respond to previous neuroleptic therapy. Reports of extrapyramidal side effects are minimal, and no case reports of tardive dyskinesia have been published. Indeed, clozapine has been used to treat tardive dyskinesia and other movement disorders. Agranulocytosis is the major adverse effect and its prevalence appears to differ among various ethnic groups. Other adverse effects that have been reported include hypersalivation, orthostatic hypotension, and constipation. Clozapine can lower the seizure threshold in a dose-dependent manner. The drug represents a significant advancement in the treatment of mental illness.
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PMID:Clozapine. 167 65

Clomipramine is a newly marketed tricyclic antidepressant drug prescribed for obsessive-compulsive disorder (OCD). It selectively blocks neuronal uptake of serotonin. Clomipramine has been prescribed in Europe and Canada for 20 years in management of depression. Studies have now shown clomipramine to be effective in treating OCD. Dry mouth, visual disturbances, constipation, sexual dysfunction, somnolence, tremors, and dizziness are among the commonly reported side effects. Like other tricyclics, clomipramine exhibits a potential for cardiotoxicity, especially by impairing conduction and/or orthostasis. It also has the effect of lowering seizure threshold. Overdose risk is considerable. Careful medical supervision and adherence to prescribing guidelines are presumed to reduce medication risk factors. The outstanding benefit of this drug is its proved efficacy in the management of obsessive-compulsive disorder, as the first pharmacotherapy approved for this previously rather treatment-resistant condition.
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PMID:Clomipramine for obsessive-compulsive disorder: prescribing guidelines. 192 26

Twenty children aged 2 months to 18 years were included in a dose-response study of vigabatrin as add-on therapy to preexisting antiepileptic drugs (up to two per patient). All children had severe refractory epilepsy: partial seizures with or without secondary generalization in 19, and myoclonic seizures in one. After a 2-month observation period and a 1-month add-on placebo period, a fixed dose of add-on vigabatrin was given for 2 months: 1, 1.5, or 2 g/day, according to body weight (mean dose, 60 mg/kg/day). Three patients (15%) became seizure free, and nine (45%) showed a 50% to 99% reduction in seizure frequency. In the 17 patients whose seizures were not totally suppressed, vigabatrin dose was increased for a further 2 months, and in 7 patients who still showed less than 50% reduction in seizure frequency, vigabatrin dose was increased again. Efficacy appeared unchanged by these higher doses. During a 9-month follow-up phase, no tolerance to the effects of vigabatrin was observed, with three children seizure free and 13 (65%) reporting a 50% to 99% reduction in seizure frequency. During the study, adverse effects were recorded in three children (15%), namely drowsiness, constipation, fatigue, and apathy. These effects were generally transient, being observed during the dose-modification phase and disappearing either spontaneously or on reduction of vigabatrin dose. Clinical and laboratory tolerability to vigabatrin appeared to be very good, with no patients having withdrawn from the study because of side effects. A slight reduction in red blood cell count and hemoglobin levels was noted but was of doubtful clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-response study of vigabatrin in children with refractory epilepsy. 194 Jan 24

Sixty-five cases of mental depression were treated with maprotiline (Ludiomil), including 46 cases of endogenous depression, 18 cases of neurotic depression and 1 case of depression in association with hypertension and cerebral arteriosclerosis. Ludiomil of 50-200 mg/d was given for 4 weeks and clinical pictures evaluated weekly. Clinical results showed complete recovery in 33 cases (50%), improvement in 22 cases (34%), fair in 7 cases (11%) and poor in 3 cases (5%). Dry mouth, constipation and faintness were the commonest side effects. Seizure occurred in 1 case and skin rash in 3 cases. The authors suggest that Ludiomil at a maximal dosage of 150 mg/d can be considered a relatively safe and effective antidepressant.
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PMID:Maprotiline (Ludiomil) treatment of mental depression--a clinical report of 65 cases. 259 36

At the eve of its mapping, the pre-molecular picture of the FG syndrome is heavily biased towards the severe end of the phenotypic spectrum because present knowledge is largely based on propositi. It is an X-linked, incompletely recessive, complexly pleiotropic syndrome with considerably variable expressivity. Though a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome, severe malformations are uncommon and involve mostly the anus (60%) and non-colonic GI defects (33%), hypospadias (25%), cleft palate (6%), rarely a congenital heart defect. The complex CNS dysfunctions of congenital hypotonia and all of its sequelae, MR, and occasional seizures, must be attributed to a developmental CNS defect which is rarely demonstrated at pre-mortem, and which is known to involve agenesis of the corpus callosum in some 25% of appropriately studied patients (mostly propositi). Thus, the diagnosis is largely made on a specific constellation of minor anomalies and mild malformations in a hypotonic boy with severe constipation and a very characteristic facial appearance and behavioral phenotype. In about 1/3 of cases, carrier manifestations may be detected physically. New hemizygote manifestations seen in this review of 5 new patients include abnormal eruption of teeth, diastasis between upper central incisors, apparent gynecomastia, cleft lip, and nasolacrimal and helicine fistulae. Only a half hundred or so FG syndrome patients are known, but we suspect the syndrome is much more common than realized, and because of the unfortunate recurrence risk potential, deserves careful consideration in every appropriate case. RFLP mapping studies are urged in order to aid diagnosis of "mild" cases, and prenatal and carrier detection.
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PMID:FG syndrome update 1988: note of 5 new patients and bibliography. 305 62

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.
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PMID:Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy. 351 4

In a man aged 28 years abdominal pains with constipation appeared, and were followed after 2 weeks by generalized maximal epileptic seizures, gradually progressing signs of proximal polyneuropathy, numerous brownish patches on the face and trunk, and hepatomegaly. In the urine raised levels were found of delta aminolaevulinic acid, prophobilinogen, coproporphyrins and uroporphyrins. Examination of stools demonstrated an increase of protoporphyrins and coproporphyrins, with prevalence of the former, characteristic of porphyria variegata. A gradual regression of changes was observed after treatment with high doses of propranolol and intravenous glucose infusions.
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PMID:[Porphyria variegata--a case report]. 356 76


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